6893b02484ee8fee4f575cef5379e037 pmc_33919036.pdf edf5501bfdbacb87b20411931f023cc5cfa0a8ee pmc_33919036.pdf a158c3f78ab2b21c09d47abf5405070ba8025d8a18aaa7d372d6c0a9a0693cb9 pmc_33919036.pdf Title: ctDNA-Based Liquid Biopsy of Cerebrospinal Fluid in Brain Cancer Subject: The correct characterisation of central nervous system (CNS) malignancies is crucial for accurate diagnosis and prognosis and also the identification of actionable genomic alterations that can guide the therapeutic strategy. Surgical biopsies are performed to characterise the tumour; however, these procedures are invasive and are not always feasible for all patients. Moreover, they only provide a static snapshot and can miss tumour heterogeneity. Currently, monitoring of CNS cancer is performed by conventional imaging techniques and, in some cases, cytology analysis of the cerebrospinal fluid (CSF); however, these techniques have limited sensitivity. To overcome these limitations, a liquid biopsy of the CSF can be used to obtain information about the tumour in a less invasive manner. The CSF is a source of cell-free circulating tumour DNA (ctDNA), and the analysis of this biomarker can characterise and monitor brain cancer. Recent studies have shown that ctDNA is more abundant in the CSF than plasma for CNS malignancies and that it can be sequenced to reveal tumour heterogeneity and provide diagnostic and prognostic information. Furthermore, analysis of longitudinal samples can aid patient monitoring by detecting residual disease or even tracking tumour evolution at relapse and, therefore, tailoring the therapeutic strategy. In this review, we provide an overview of the potential clinical applications of the analysis of CSF ctDNA and the challenges that need to be overcome in order to translate research findings into a tool for clinical practice. Keywords: central nervous system malignancies; brain cancer; circulating tumour DNA; cerebrospinal fluid; liquid biopsies Author: Laura Escudero, Francisco Martínez-Ricarte and Joan Seoane Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Apr 21 08:18:58 2021 CEST ModDate: Wed Apr 21 08:33:05 2021 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 15 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1318802 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- PLSPPH+VnURWPalladioL Type 1 Custom yes yes no 10 0 IEHSWL+URWPalladioL-Ital Type 1 Custom yes yes no 15 0 WPLUMY+URWPalladioL-Bold Type 1 Custom yes yes no 20 0 BAWJGF+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 WLENKM+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 LCJEVJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 37 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 59 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 63 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 67 0 ABCDEE+Palatino Linotype,Bold TrueType WinAnsi yes yes no 86 0 ABCDEE+Palatino Linotype TrueType WinAnsi yes yes no 90 0 ABCDEE+Palatino Linotype,Italic TrueType WinAnsi yes yes no 94 0 ABCDEE+Palatino Linotype CID TrueType Identity-H yes yes yes 98 0 ABCDEE+Palatino Linotype,Bold TrueType WinAnsi yes yes no 129 0 ABCDEE+Palatino Linotype TrueType WinAnsi yes yes no 133 0 ABCDEE+Palatino Linotype,Italic TrueType WinAnsi yes yes no 137 0 ABCDEE+Palatino Linotype CID TrueType Identity-H yes yes yes 141 0 PDTLUH+CMSY10 Type 1 Builtin yes yes no 156 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2021-09-11 03:26:19 CEST RepresentationInformation: pmc_33919036.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2021-05-17 03:36:12 CEST Size: 1318802 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 522 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Circulating Cell-Free DNA and Circulating Tumour DNA Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Cerebrospinal Fluid as a Source of ctDNA Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Clinical Applications of the CSF ctDNA for CNS Malignancies Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Children: Item: Title: Diffuse Gliomas Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Children: Item: Title: A Diagnostic and Prognostic Tool Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Monitoring and Therapeutic Strategies Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Brain and Leptomeningeal Metastases Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Children: Item: Title: CSF ctDNA Facilitates Diagnosis and Allows Tumour Genomic Characterisation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Patient Monitoring and Identification of Therapeutic Targets Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: CNS Lymphoma Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: Medulloblastoma Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: Challenges and Limitations Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: Conclusions and Future Insights Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Info: Title: ctDNA-Based Liquid Biopsy of Cerebrospinal Fluid in Brain Cancer Author: Laura Escudero, Francisco Martínez-Ricarte and Joan Seoane Subject: The correct characterisation of central nervous system (CNS) malignancies is crucial for accurate diagnosis and prognosis and also the identification of actionable genomic alterations that can guide the therapeutic strategy. Surgical biopsies are performed to characterise the tumour; however, these procedures are invasive and are not always feasible for all patients. Moreover, they only provide a static snapshot and can miss tumour heterogeneity. Currently, monitoring of CNS cancer is performed by conventional imaging techniques and, in some cases, cytology analysis of the cerebrospinal fluid (CSF); however, these techniques have limited sensitivity. To overcome these limitations, a liquid biopsy of the CSF can be used to obtain information about the tumour in a less invasive manner. The CSF is a source of cell-free circulating tumour DNA (ctDNA), and the analysis of this biomarker can characterise and monitor brain cancer. Recent studies have shown that ctDNA is more abundant in the CSF than plasma for CNS malignancies and that it can be sequenced to reveal tumour heterogeneity and provide diagnostic and prognostic information. Furthermore, analysis of longitudinal samples can aid patient monitoring by detecting residual disease or even tracking tumour evolution at relapse and, therefore, tailoring the therapeutic strategy. In this review, we provide an overview of the potential clinical applications of the analysis of CSF ctDNA and the challenges that need to be overcome in order to translate research findings into a tool for clinical practice. 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